Endoprosthesis structures having supporting features

ABSTRACT

An endoprosthesis includes a plurality of serpentine rings having supporting features which increase hoop strength, inhibit recoil, and provide an increased surface area. The supporting features may be formed between adjacent axial struts of the serpentine rings or may be positioned between axial lengths joining the serpentine rings together.

CROSS REFERENCES TO RELATED APPLICATIONS

This application claims the benefit of provisional application60/885,700 (Attorney Docket No. 022265-000500US), filed on Jan. 19,2007, the full disclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to endoprosthesis designs, in particularbiodegradable and non-biodegradable stents and grafts, which are adaptedto be implanted into a patient's body lumen, such as coronary artery orother blood vessel or body lumen. Stents are particularly useful in thetreatment of atherosclerotic stenosis in arteries and veins.

Stents are generally tubular-shaped devices which function to hold openor reinforce a segment of a blood vessel or other body lumen such as acoronary artery, carotid artery, saphenous vein graft, or femoralartery. They also are suitable to support and hold back a dissectedarterial lining that can occlude the fluid passageway, to stabilizeplaque, or to support bioprosthetic valves. Stents can be formed fromvarious materials, particularly polymeric and/or metallic materials, andmay be non-degradable, biodegradable, or be formed from both degradableand non-degradable components. Stents are typically delivered to thetarget area within the body lumen using a catheter. Withballoon-expandable stents, the stent is mounted to a balloon catheter,navigated to the appropriate area, and the stent expanded by inflatingthe balloon. A self-expanding stent is delivered to the target area andreleased, expanding to the required diameter to treat the disease.Stents may also elute various drugs and pharmacological agents.

Referring to FIG. 1, a common pattern employed in present cardiovascularstents comprises a plurality of serpentine rings 12 joined by shortaxial links 14. The serpentine rings comprise axial struts 16, wherecircumferentially adjacent struts are connected by crowns 18 which actas hinges in permitting circumferential expansion of the individualrings 12. These patterns can be used for both degradable andnon-degradable stents and other endoprostheses.

In the design of stents and other endoprostheses, a number of competingobjectives must be addressed. For coronary artery stents, it is usuallydesirable to be able to collapse the stent to minimize thecross-sectional area for delivery while maximizing the surface area ofthe stent after expansion. A maximized surface area provides bothenhanced wall support to reduce vessel recoil and a greater capacity todeliver drugs when employing drug-coated stents. A further designobjective is to allow the stent to be compressed with a minimum forcewhile still maintaining a good hoop strength after expansion to furtherresist vessel recoil.

Thus, what is needed is a stent design or stent material which enhancesradial or hoop strength, reduces vessel recoil after implantation,provides an increased surface area while maintaining or reducing thesize and mass of the stent. The present invention meets at least some ofthese requirements.

2. Description of the Background Art

U.S. Pat. No. 6,773,455 describes a stent having serpentine ringsaxially connected via internal expansion elements. US 2003/0093143describes a stent comprising box structures joined circumferentially byU-shaped connectors. US2003/0144729 describes a stent comprising axiallyspaced serpentine bands connected by wishbone connectors. See also U.S.Pat. No. 7,291,166 and U.S. Pat. No. 6,896,695.

SUMMARY OF THE INVENTION

The present invention provides an endoprosthesis, such as a stent, graftor other scaffold-like luminal prosthesis, that is used for treatingvascular and other luminal conditions. The endoprosthesis includessupporting features or elements added to a base structure. The basestructure of the stent is formed from a series of circumferentialserpentine rings connected directly to each other or with at least onelink or strut, generally as shown in FIG. 1 discussed above, where eachring comprises multiple expansion segments constructed from crowns andstruts. In accordance with the present invention, the base structure isreinforced with supporting features which can increase radial strengthand/or reduce recoil upon expansion of the stent compared to thestructure without the supporting features. The supporting features cancontain varying types of shapes such as an I-shape, C-shape, V-shape,U-shape, S-shape, Y-shape, M-shape, W-shape, Z-shape, spiral-shape orother types. In a first embodiment, the supporting features connect atleast some of the adjacent struts. In another embodiment at least onesupporting feature connects to at least one axially connecting link.

Thus, according to the present invention, an endoprosthesis comprises aplurality of circumferentially expandable serpentine rings, axial linksjoining the adjacent rings, and supporting features. Thecircumferentially expandable serpentine rings each include axial strutsjoined by crowns, where the crowns act as hinges allowing the struts tospread as the ring opens circumferentially. The axial links join theadjacent serpentine rings by connecting at least some of the crowns onthe rings. The supporting features extend between at least some of theadjacent struts of at least some of the serpentine rings, where thesupporting features elongate and the struts remain substantiallyundeformed as the ring circumferentially expands.

The endoprosthesis may be constructed from a variety of conventionalstent materials and may be either balloon-expandable, self-expanding, ora combination of both. The serpentine rings of the self-expandingendoprostheses will be sufficiently elastic so that they can beconstrained in a small cross-sectional area during delivery and releasedwithin the vasculature or other body lumens to assume acircumferentially expanded configuration. In contrast, the serpentinerings of the balloon-expandable endoprostheses will be sufficientlymalleable so that they can be circumferentially expanded by applying aradially outward force from within the rings, typically using aninflatable balloon or other expandable structure. Particularly preferredstent materials include metals and alloys such as iron, zinc, steel,cobalt-chromium, nickel-titanium, as well as polymers such as polylactides, polycaprolactone, polyethylene carbonate, copolymers ofpolylactide-glycolide, poly lactide-trimethylenecarbonates, and thelike. Particular materials and fabrication methods are described incommonly owned application Ser. No. 11/______ (Attorney Docket No.022265-000520US), filed on the same day as the present application.

The supporting features may have a variety of specific configurations orpatterns which are selected to elongate or otherwise expand as theserpentine rings of the endoprosthesis are expanded. Exemplarysupporting feature configurations include U-shaped connectors, V-shapedconnectors, S-shaped connectors, spiral-shaped connectors, W-shapedconnectors, N-shaped connectors, Z-shaped connectors, and the like. Inorder to increase or control the exposed surface area of theendoprosthesis, the supporting structures may have variable widths, forexample the spiral-shaped connectors may include ring or disk-shapedcores to enhance or control the surface area. While the width andcross-sectional area of the supporting feature will usually be less thanthe width and cross-sectional area of the serpentine rings so thatexpansion of the supporting features does not deform or deflect the mainring structure, it will be possible to increase the area of thesupporting feature by providing deflection points which allow thesupporting feature to yield preferentially relative to the serpentinerings. For example, portions of the supporting feature may be notched sothat they yield first as the endoprosthesis is expanded.

In some embodiments, one or more additional supporting features may bedisposed between at least some of the adjacent struts. When a singlesupporting feature is employed, it will usually extend generally betweenthe mid-points on the adjacent struts, but in other instances could bedisposed closer to the ends of the struts which are not connectedtogether with a crown. In cases where two or more supporting featuresare provided between adjacent pairs of struts, they may be located atany point along the length of the strut, typically with one beinglocated near the midpoint and another being located near the free ends(i.e., ends which are not joined together with the crown).

The axial links will usually comprise short linear beams, where thelinear beams are axially aligned with the axis of the endoprosthesis. Inother cases, the linear beams may be aligned at a shallow angle relativeto the axis, typically from zero degrees to 45 degrees.

Endoprostheses according to the present invention may comprise aplurality of circumferentially expandable serpentine rings joined byaxial links, where the supporting features extend between at least someadjacent axial links between adjacent serpentine rings. These supportingfeatures between the adjacent axial links elongate as the ringscircumferentially expand. Exemplary supporting features which areconnected between the adjacent axial links include serpentineconnectors, usually where folded portions of the connectors extend intothe region between adjacent axial struts. Alternatively, the connectorscould comprise “box” connectors having symmetric extending lengths whichproject into the regions between axial struts.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a conventional serpentine ring stent.

FIGS. 2A and 2B illustrate a first embodiment of the endoprostheses ofthe present invention having U-shaped connectors between adjacent axialstruts in a serpentine ring.

FIG. 3 illustrates the stent structure of FIGS. 2A and 2B afterexpansion.

FIGS. 4 and 5 illustrate an exemplary V-shaped connector as thesupporting feature where the connector can be oriented toward the crown(FIG. 4) or away from the crown (FIG. 5).

FIG. 6 illustrates an exemplary S-shaped connector as the supportingstructure.

FIGS. 7-9 illustrate exemplary spiral-shaped supporting structures,where FIG. 7 illustrates an everting spiral, FIG. 8 illustrates a spiralhaving a ring core, and FIG. 9 illustrates a spiral having a disk core.

FIG. 10 illustrates an exemplary endoprosthesis structure havingU-shaped connectors located near the open ends of the serpentinestructure.

FIGS. 11 and 12 illustrate exemplary endoprosthesis structures havingpairs of supporting features between adjacent axial struts.

FIG. 13 illustrates a complex supporting feature having both radiallyand axially aligned elongating portions.

FIGS. 14, 15A and 15B illustrate a U-shaped supporting feature havingnotch-like yield points which control a two-stage expansion, as shown inFIGS. 15A and 15B.

FIGS. 16 and 17 illustrate exemplary endoprosthesis designs whereadjacent serpentine rings are connected by angled axial links. FIG. 16further illustrates an M-shaped connector as the supporting featurewhile FIG. 17; illustrates a N-shaped connector as the supportingfeature.

FIGS. 18 and 19 illustrate supporting features connecting adjacent axiallinks, where FIG. 18 illustrates a serpentine pattern, FIG. 19illustrates a box pattern connector.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an endoprosthesis, such as a stent, thatis used for treating vascular or other luminal conditions withsupporting features or elements added to a base stent structure. Thebase structure of the stent is formed from one or more serpentine rings.The rings may be interconnected directly or with at least one link. Eachring is composed of multiple expansion segments constructed from crownsand struts. The stent is then reinforced by supporting features thatincrease radial strength (e.g., hoop strength), increase surface area,and/or reduce recoil compared to the stent without the supportingfeatures. The at least one supporting feature usually connects oppositesides of axial struts which expand (spread apart) about crowns (hinges).Alternatively, the supporting feature may connect axial links which jointhe serpentine rings. Upon expansion of the segment the supportingfeature increases radial strength and/or reduces recoil. The stents maybe non-degradable or degradable, where degradation includesbiodegradation, bioerosion, bioabsorption, corrosion, and disintegrationcompletely or partially in physiological environment. The supportingfeature may undergo plastic deformation upon expansion to reinforce thebase structure of the stent or alternatively may elastically expand toprovide the reinforcement.

In one embodiment the at least one supporting feature undergoesdeformation upon expansion and reinforces the base structure of thestent. Usually the at least one supporting feature increases the radialstrength of the expanded stent by at least 15%, preferably by at least50%, more preferably by at least 100% compared to the stent without theat least one supporting feature. In other embodiments the at least onesupporting feature provides a stent which recoils after expansion byless than 15%, preferably by less than 7%, more preferably by less than4%. In one instance, the at least one supporting feature provides astent with recoil at least 28 days after expansion in a mammal of lessthan 20%, preferably less than 10%, more preferably less than 6%.

The supporting features will usually connect from strut to strut, butmay alternatively or additionally from strut to crown, from strut tolink, from link to link, from crown to crown, from crown to link, orfrom crown to same crown. Exemplary supporting features can containvarying types of shapes such as C-shape, V-shape, U-shape, S-shape,Y-shape, M-shape, W-shape, Z-shape, spiral-shape or other types. Theseshapes may be continuous or discontinuous. At least one type ofsupporting feature per ring may be present.

The supporting feature thickness and/or width may be greater than, lessthan or approximately equal to the thickness of the adjacent expansionsegment. In one embodiment the supporting feature thickness ranges from0.125 mm (0.0005 in) to 2.5 mm (0.010 in), preferably 0.25 mm (0.001 in)to 1.25 mm (0.005 in), more preferably 0.5 mm (0.002 in) to 1 mm (0.004in). In one embodiment the supporting feature width ranges from 0.125 mm(0.0005 in) to 2.5 mm (0.010 in), preferably 0.25 mm (0.001 in) to 1.25mm (0.005 in), more preferably 0.5 mm (0.002 in) to 1 mm (0.004 in). Inone embodiment the path length of the supporting feature ranges from1.25 mm (0.005 in) to 25 mm (1 in), preferably 0.25 mm (0.010 in) to0.75 mm (0.250 in), more preferably 0.5 mm (0.020 in) to 2.5 mm (0.100in).

In one embodiment the angle at which the supporting feature connects tothe expansion segment or link is approximately 90 degrees, but the anglemay alternatively be less than 90 degrees or greater than 90 degrees.Usually, the angle at which the supporting feature connects to the axialstrut or link ranges from 30 degrees to 150 degrees, preferably 45 to135 degrees, more preferably 60 to 120 degrees.

The material of the supporting feature may be metallic, metal alloy,polymeric, composite, ceramic, or combination thereof, or other type ofmaterial, and can be of similar type as the expansion segment or link,or different type.

The increase in radial strength and/or reduction of recoil provided bythese designs can be of particular benefit for biodegradable stents. Theendoprosthesis designs and patterns are applicable to both biodegradableand non-biodegradable materials to provide an enhanced strength and/orincreased elasticity. Exemplary biodegradable endoprosthesis materialsinclude metallic, metallic alloy, polymeric, ceramic, composite, as wellas other materials in combinations thereof. The yield strength for thebiodegradable material(s) will usually be at least 50% of ultimatestrength, preferably being at least 75% of ultimate strength, and morepreferably being at least 90% of ultimate strength. For biodegradablepolymeric stent materials, the yield strength can be measured in waterat 37° C. The elastic modulus for biodegradable metallic stents willusually be at least 50 GPa, preferably being at least 100 GPa, and morepreferably at least 150 GPa. The elastic modulus of biodegradablepolymeric stents, in contrast, will be at least 0.5 GPa, preferablybeing at least 0.75 GPa, and more preferably being at least 1 GPa,measured in water at 37° C. Higher strain at yield may contribute togreater recoil of the stent. The yield strain for biodegradablepolymeric stent materials will preferably be no more than 10% whenmeasured in water at 37° C., preferably being no more than 5%, and morepreferably being no more than 3%. The plastic strain for thebiodegradable polymeric stent materials will preferably be at least 20%,more preferably being at least 30%, and still more preferably being atleast 40%, when measured in water at 37° C., while the elastic recoveryof the strained biodegradable polymeric stent material is at most 15%,preferably at most 10%, and more preferably at most 5%, when measured inwater at 37° C.

The biodegradable stent materials may have a widely varying persistence.Usually, the material will substantially degrade within three yearsafter implantation, more usually within one year, and still more usuallywithin six months. When degrading under physiological conditions, suchas vascular conditions, after one month the biodegradable stent willpreferably retain at least 25% of the hoop strength, preferablymaintaining at least 40%, and more preferably maintaining at least 70%.

The biodegradable polymeric stent materials may degrade by any ofseveral known mechanisms, including bulk erosion, surface erosion, andcombinations thereof. The biodegradable polymeric stent material usuallydegrades by at least one of hydrolytic degradation, enzymaticdegradation, oxidative degradation, photo degradation, degradation underphysiological environment or combination thereof.

Suitable the biodegradable polymeric stent material includes, but arenot limited to, polyesters, polyanhydrides, polyamides, polyurethanes,poly(ester urethane), polyureas, polyethers, polyalkylene carbonates,polyacrylic acids, polyamines, polyester amides, polyester amines,polyvinylacetate, polyethylene imine, polycyanoacrylates,polyphosphazenes, polyphosphates, polyphosphonates, polyurethanes,polyureas, polysulfonates, polysulfonamides, polylactides,polyglycolides, regenerated cellulose, or biopolymers or blends, blockpolymers, copolymers or combinations thereof. Examples of these polymersinclude but are not limit to poly(L-lactic acid), poly(L/D-lactic acid),poly(L/DL-lactic acid), poly(glycolic acid), poly(lactide-co-glycolide),and copolymers and isomers, polydioxanone, poly(ethyl glutamate),poly(hydroxybutyrate), polyhydroxyvalerate and copolymer poly(3-hydroxybutyrate-co-hydroxy valerate), polycaprolactone, polyanhydride,poly(ortho esters); poly(ether esters), poly(trimethyl carbonate),Poly(L-lactic acid-co-trimethylene carbonate), Poly(L/D-lacticacid-co-trimethylene carbonate), Poly(L/DL-lactic acid-co-trimethylenecarbonate), Poly(caprolactone-co-trimethylene carbonate), Poly(glycolicacid-co-trimethylene carbonate), Poly(glycolic acid-co-trimethylenecarbonate-co-dioxanone), polyethylene carbonate, copolymers ofpolyethylene carbonate and poly(trimethylene carbonate), polypropylenecarbonate, poly (iminocarbonates), poly(malic acid), modifiedpoly(ethylene terephthalate), poly(butylene succinate), poly(butylenesuccinate adipate), poly(butylene succinate terephthalate),poly(butylene adipate-co-terephthalate), starch based polymers,hylaronic acid, oxidized or non-oxidized regenerated cellulosecopolymers and other aliphatic polyesters, or suitable copolymersthereof. The biodegradable polymeric stent material in this inventioncan be homopolymers, copolymers, graft polymer, block polymers, polymerswith special functional groups or end groups such as acidic orhydrophilic type or a blend of two or more homopolymers or copolymers.

The biodegradable polymeric stent material can have varying moleculararchitecture such as linear, branched, crosslinked, hyperbranched ordendritic. The biodegradable polymeric stent material in this inventioncan range from 10 KDa to 10,000 KDa in molecular weight, preferably from100 KDa to 1000 KDa, more preferably 300 KDa to 600 KDa.

In certain embodiments, the biodegradable polymeric stent materialincorporates at least one additive. The additives can affect strength,recoil, or degradation rate or combination thereof. Additives can alsoaffect processing of biodegradable stent material, radiopacity orsurface roughness or others. Additives can be biodegradable ornon-biodegradable. The additives can be incorporated in to thebiodegradable stent material by blending, extrusion, injection moulding,coating, surface treatment, chemical treatment, mechanical treatment,stamping, or others or combinations thereof. The additives can bechemically modified prior to incorporation in to the biodegradable stentmaterial.

In one embodiment, the weight percentage of the additives can range from0.01% to 25%, preferably 0.1% to 10%, more preferably 1% to 5%. In oneembodiment, the additive includes at least nanoclay, nanotubes,nanoparticles, exfoliates, fibers, whiskers, platelets, nanopowders,fullerenes, nanosperes, zeolites, polymers or others or combinationthereof. Examples of nanoclay includes Montmorillonite, Smectites, Talc,or platelet-shaped particles or others or combination thereof. Clays canbe intercalated or exfoliated. Example of clays include Cloisite NA,93A, 30B, 25A, 15A, 10A or others or combination thereof. Examples offibers include cellulose fibers such as Linen, cotton, rayon, acetate;proteins fibers such as wool or silk; plant fiber; glass fiber; carbonfiber; metallic fibers; ceramic fibers; absorbable fibers such aspolyglycolic acid, polylactic acid, polyglyconate or others. Examples ofwhiskers include hydroxyapetite whiskers, tricalcium phosphate whiskersor others.

In another embodiment, the additives includes at least modified starch,soybean, hyaluronic acid, hydroxyapatite, tricarbonate phosphate,anionic and cationic surfactants such as sodium docecyl sulphate,triethylene benzylammonium chloride, pro-degradant such as D2W (fromSymphony Plastic Technologies), photodegradative additives such as UV-H(from Willow Ridge Plastics), oxidative additives such as PDQ (fromWillow Ridge Plastics), TDPA, family of polylactic acid and its randomor block copolymers or others.

In another embodiment, the additive can induce degradation ofnon-degradable polymeric stent material. For example pro-degradant suchas D2W (from Symphony Plastic Technologies), photodegradative additivessuch as UV-H (from Willow Ridge Plastics), oxidative additives such asPDQ (from Willow Ridge Plastics), TDPA or others or combination thereofcan initiate degradation of non degradable stent materials such aspolyethylene, polypropylene, polyethylene terephthalate or others. Instill other embodiments, the additives include electroactive orelectrolyte polymers, hydroscopic polymers, dessicants, or others. Theadditive may include an oxidizer such an acids, perchlorates, nitrates,permanganates, salts or other or combination thereof. The additive mayinclude a monomer of the biodegradable polymeric stent material. Forexample glycolic acid is an additive to polyglycolic acid or itscopolymer stent material. The additive may include water repellentmonomers, oligomers or polymers such as bees wax, low MW polyethylene orothers. In other embodiments, the additive can be water attractantmonomers, oligomers or polymers such as polyvinyl alcohol, polyethyleneoxide, glycerol, caffeine, lidocaine or other. In other embodiments, theadditive can affect crystallinity of the biodegradable polymeric stentmaterial. Example of additive of nanoclay to PLLA affects itscrystallinity. In still other embodiments, the biodegradable polymericstent material can have increased crystallinity upon exposure toradiation such as gamma or ebeam. The cumulative radiation dose canrange from 1 Mrad to 100 Mrad, preferably 5 to 50 Mrad, more preferably10 to 30 Mrad. The biodegradable stent material has increasedcrystallinity by increasing orientation of polymer chains with in thebiodegradable stent material in radial and/or longitudinal direction bydrawing, pressurizing and/or heating the stent material. In anotherembodiment, the drawing, pressurizing and/or heating the stent materialoccurs simultaneously or sequentially.

Specific methods for preparing biodegradable polymeric stents having thepatterns disclosed herein are described in copending application Ser.No. 11/______ (Attorney Docket No. 022265-000520US), filed on the sameday as the present application, all disclosure of which is incorporatedherein by reference.

In the present invention, the stent material may include pharmacologicalagents, such as immunomodulators, anti-cancer, anti-proliferative,anti-inflammatory, antithrombotic, antiplatelet, antifungal,antidiabetic, antihyperlipidimia, antiangiogenic, angiogenic,antihypertensive, healing promoting drugs, or other therapeutic classesof drugs or combination thereof. Illustrative immunomodulators agentsinclude but are not limited to rapamycin, everolimus, ABT 578, AP20840,AP23841, AP23573, CCl-779, deuterated rapamycin, TAFA93, tacrolimus,cyclosporine, TKB662, myriocin, their analogues, pro-drug, metabolites,slats, or others or combination thereof.

Illustrative anticancer agents include acivicin, aclarubicin, acodazole,acronycine, adozelesin, alanosine, aldesleukin, allopurinol sodium,altretamine, aminoglutethimide, amonafide, ampligen, amsacrine,androgens, anguidine, aphidicolin glycinate, asaley, asparaginase,5-azacitidine, azathioprine, Bacillus calmette-guerin (BCG), Baker'sAntifol (soluble), beta-2′-deoxythioguanosine, bisantrene hcl, bleomycinsulfate, busulfan, buthionine sulfoximine, BWA 773U82, BW 502U83.HCl, BW7U85 mesylate, ceracemide, carbetimer, carboplatin, carmustine,chlorambucil, chloroquinoxaline-sulfonamide, chlorozotocin, chromomycinA3, cisplatin, cladribine, corticosteroids, Corynebacterium parvum,CPT-11, crisnatol, cyclocytidine, cyclophosphamide, cytarabine,cytembena, dabis maleate, dacarbazine, dactinomycin, daunorubicin HCl,deazauridine, dexrazoxane, dianhydrogalactitol, diaziquone,dibromodulcitol, didemnin B, diethyldithiocarbamate, diglycoaldehyde,dihydro-5-azacytidine, doxorubicin, echinomycin, edatrexate, edelfosine,eflomithine, Elliott's solution, elsamitrucin, epirubicin, esorubicin,estramustine phosphate, estrogens, etanidazole, ethiofos, etoposide,fadrazole, fazarabine, fenretinide, filgrastim, finasteride, flavoneacetic acid, floxuridine, fludarabine phosphate, 5-fluorouracil,Fluosol®, flutamide, gallium nitrate, gemcitabine, goserelin acetate,hepsulfam, hexamethylene bisacetamide, homoharringtonine, hydrazinesulfate, 4-hydroxyandrostenedione, hydrozyurea, idarubicin HCl,ifosfamide, interferon alfa, interferon beta, interferon gamma,interleukin-1 alpha and beta, interleukin-3, interleukin-4,interleukin-6,4-ipomeanol, iproplatin, isotretinoin, leucovorin calcium,leuprolide acetate, levamisole, liposomal daunorubicin, liposomeencapsulated doxorubicin, lomustine, lonidamine, maytansine,mechlorethamine hydrochloride, melphalan, menogaril, merbarone,6-mercaptopurine, mesna, methanol extraction residue of Bacilluscalmette-guerin, methotrexate, N-methylformamide, mifepristone,mitoguazone, mitomycin-C, mitotane, mitoxantrone hydrochloride,monocyte/macrophage colony-stimulating factor, nabilone, nafoxidine,neocarzinostatin, octreotide acetate, ormaplatin, oxaliplatin,paclitaxel, pala, pentostatin, piperazinedione, pipobroman, pirarubicin,piritrexim, piroxantrone hydrochloride, PIXY-321, plicamycin, porfimersodium, prednimustine, procarbazine, progestins, pyrazofurin, razoxane,sargramostim, semustine, spirogermanium, spiromustine, streptonigrin,streptozocin, sulofenur, suramin sodium, tamoxifen, taxotere, tegafur,teniposide, terephthalamidine, teroxirone, thioguanine, thiotepa,thymidine injection, tiazofurin, topotecan, toremifene, tretinoin,trifluoperazine hydrochloride, trifluridine, trimetrexate, tumornecrosis factor, uracil mustard, vinblastine sulfate, vincristinesulfate, vindesine, vinorelbine, vinzolidine, Yoshi 864, zorubicin,QP-2, epothilone D, epothilone C Taxol, such as, paclitaxel, docetaxel,ABJ879, patupilone, MN-029, BMS247550, ecteinascidins such as ET-743,tetrahydroisoquinoline alkaloid, sirolimus, actinomycin, methotrexate,antiopeptin, vincristine, mitomycin, 2-chlorodeoxyadenosine or others,antifungal agents such as caspofungin, farnesylated dibenzodiazepinone,ECO-4601, fluconazole, or others, angiogenesis drugs such asfollistatin, leptin, midkine, angiogenin, angiopoietin-1, becaplermin,Regranex, anti-angiogenesis drugs such as canstatin, angiostatin,endostatin, retinoids, tumistatin, vasculostatin, angioarrestin,vasostatin, bevacizumab, prinomastat, or others, antidiabetic drugs suchas metformin, hypertension drugs such as candesartan, diovan, diltiazem,atenolol, adalat or others, anti-ischemia drugs such as ranolazine,isosorbide dinitrate, or others.

Illustrative antiinflammatory agents include classic non-steroidalanti-inflammatory drugs (NSAIDS), such as aspirin, diclofenac,indomethacin, sulindac, ketoprofen, flurbiprofen, ibuprofen, naproxen,piroxicam, tenoxicam, tolmetin, ketorolac, oxaprosin, mefenamic acid,fenoprofen, nambumetone (relafen), acetaminophen (Tylenol®), andmixtures thereof, COX-2 inhibitors, such as nimesulide, NS-398,flosulid, L-745337, celecoxib, rofecoxib, SC-57666, DuP-697, parecoxibsodium, JTE-522, valdecoxib, SC-58125, etoricoxib, RS-57067, L-748780,L-761066, APHS, etodolac, meloxicam, S-2474, and mixtures thereof,glucocorticoids, such as hydrocortisone, cortisone, prednisone,prednisolone, methylprednisolone, meprednisone, triamcinolone,paramethasone, fluprednisolone, betamethasone, dexamethasone,fludrocortisone, desoxycorticosterone, fluticasone propionate,piroxicam, celeoxib, mefenamic acid, tramadol, meloxicam, methylprednisone, pseudopterosin, or others, hypercalcemia drugs such aszoledronic acid, alendronate or others, antithrombosis drugs likeplavix, heparin, Arixtra and Fraxiparine or others or mixtures thereof.

Use of analogues, prodrugs, derivatives, precursors, fragments, salts,or other modifications or variations of pharmaceutical agents are allincluded.

Analogs, derivatives, prodrugs, salts, synthetic or biologic equivalentsof these pharmaceutical agents can be released from the stents dependingon the type of treatment needed, such as hyperproliferative diseases,stenosis, wound healing, cancer, aneurysm, diabetic disease, abdominalaortic aneurysm, angiogenesis, hypercalcemia, ischemia, fibrillation,arrhythmia or others.

The agents can be released from the implant using non-degradable,partially degradable, fully degradable coatings or a combination asdisclosed in prior patent application which is referenced andincorporated in this application in its entirety. The agents can beincorporated as a matrix with the coating or applied on the stent andcovered with the coating as a rate limiting barrier, or the drug agentdirectly coated onto the stent surface.

The solvent used to incorporate the agent and the coating on a stent canbe an organic solvent such as dichloromethane, tetrahydrofuran, ethanol,or other solvents. In one embodiment, the solvent used to coat the agentand/or agent-polymer matrix does not affect the chemical or mechanicalproperties of the polymeric stent material.

In one embodiment, supercritical fluids such as supercritical carbondioxide is used as a carrier solvent for the agent and/or the polymerand coats the stent with agent and/or agent-polymer matrix. The use ofnon-reactive gas such as carbon dioxide removes the need to use otherorganic solvents which can alter chemical and physical properties of thepharmacological agent.

In one embodiment the crystallinity of the pharmaceutical agent on thestent material is greater than 90%, preferably greater than 93%, morepreferably greater than 95%.

In one embodiment, the pharmacological agent can be incorporated in thebiodegradable polymeric stent material and extruded into stent tubingprior to laser cutting of the stent from the tubes. In anotherembodiment the agent is incorporated in a protective coating to preventdegradation of the agents during extrusion or laser cutting.

In one embodiment, the rate of agent release can be configured to berelease at certain times and for certain durations corresponding to thedegradation rate of the stent material or biological response eventswithin the stent material environment. For example, ananti-inflammatory, antiproliferative, or immunomodulator drug or acombination of these can be made to release during the entiredegradation period. Multiple drugs can be released to match thedegradation rate of the coating and/or degradation rate of the implant.Antiplatelet or anti-thrombotic agents can be released in the initialphase and anti-inflammatory or antiproliferative or immunosuppressantscan be released concurrently or at the later phase.

Referring now to FIGS. 2A and 2B, a stent 10 according to the presentinvention has the same base pattern as the stent illustrated in FIG. 1,including a plurality of adjacent serpentine rings 12 joined by axiallinks 14. As illustrated, the stent 10 includes six adjacent serpentinerings 12, where each ring includes six serpentine segments comprising apair of axial struts 16 joined by a hinge-like crown 18 at one end. Thenumber of rings and segments may vary widely depending on the size ofthe desired size of the stent. According to the present invention, asupporting feature 20 is disposed between adjacent axial struts 16 andconnected so that it will expand, usually elongate, circumferentiallywith the struts, as shown in FIG. 3. The supporting features 20 are in agenerally closed U-shaped configuration prior to expansion, as shown inFIGS. 2A and 2B, and open into a shallow V-shape along with the openingof the axial struts 16 about the crowns 18 during radial expansion ofthe serpentine rings 12, as shown in FIG. 3. Supporting features 20enhance the hoop strength of the stent after radial expansion, helpresist recoil after expansion is completed, and provide additional areafor supporting the vascular or other luminal wall and optionally fordelivering drugs into the luminal wall.

While U-shaped supporting feature 20 are illustrated in FIGS. 2A and 2B,a variety of other configurations may be utilized, as illustrated inFIGS. 4-17. In FIG. 4, V-shaped supporting features 22 are disposedbetween the adjacent axial struts 16. The supporting features 24 of FIG.5 are generally the same as those in FIG. 4, except they are pointed inthe opposite direction, i.e., away from the crowns 18 rather than towardthe crowns. S-shaped connectors 26 are illustrated in FIG. 6, whilespiral-shaped connectors 28 are shown in FIG. 7. FIG. 8 shows analternative spiral-shaped connector 30 having an open ring at itscenter, while FIG. 9 shows a similar supporting feature 32 having a diskat its center.

As shown thus far, the supporting features 20-32 have been connected tothe adjacent axial struts 16 near the midpoints of said struts.Supporting features 34 may also be connected near the open ends of theaxial struts 16, as shown in FIG. 10, or may be connected in pairs or ingreater number, as shown in FIG. 11. FIG. 12 illustrates a pair ofconnectors 34 joined near the midpoint, while FIG. 13 illustrates acomplex supporting feature 40 joined between adjacent axial struts 16 atthree points, two near the open end of the struts and a third on theinner side of the crown 18.

Referring now to FIGS. 14, 15A and 15B, the supporting features 42 mayhave deflection points 44 formed along their lengths in order to controlexpansion. For example, by placing notches 44 in the middle of theU-shaped connector 42, the supporting features may be programmed tofirst open at the deflection points 44, as illustrated in FIG. 15A, andto later open at the crown of the connector, as shown in FIG. 15B. Suchprogrammed opening helps assure that the axial struts 16 may expandwithout being significantly hindered by the forces needed to expand thesupporting features 42.

Still further variations in the structure and positioning of thesupporting features and axial links may be provided. As shown in FIG.16, the supporting features 50 may comprise N-shaped connectors whilethe axial links 52 may be angled relative to the axial direction of theendoprosthesis. Similarly, as shown in FIG. 17, N-shaped supportingfeatures 60 may be provided to join serpentine rings held together byangled axial links 62.

Referring now to FIGS. 18 and 19, the supporting features may also beconnected between axial links 14 in the endoprostheses of the presentinvention. The supporting feature 70 has a generally serpentineconfiguration with a bent or folded portion extending into the regionbetween adjacent axial struts 16. The supporting feature 72 in theendoprosthesis of FIG. 19 is similar to 70, except that the supportingfeature includes a box region having a pair of projections 74 extendinginto the regions between adjacent axial struts 16. In both cases, thesupporting features 70 and 72 will both enhance the hoop strength of theserpentine ring after radial expansion, inhibit recoil, and provide anenhanced surface area for supporting tissue and delivering activeagents.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

1. An endoprosthesis comprising: a plurality of circumferentiallyexpandable serpentine rings, each serpentine ring including axial strutsjoined by crowns, wherein the crowns act as hinges allowing the strutsto spread as the ring opens circumferentially; axial links joining atleast some crowns on adjacent rings; and supporting features extendingbetween at least some adjacent struts of at least some of the serpentinerings, wherein the supporting features elongate and the struts remainsubstantially undeformed as the rings circumferentially expand.
 2. Anendoprosthesis as in claim 1, at least partially comprising abiodegradable material.
 3. An endoprosthesis as in claim 1, at leastpartially comprising a metal.
 4. An endoprosthesis as in claim 1,wherein the serpentine rings are sufficiently elastic so that they canbe constrained in a small cross-sectional area and released to assume acircumferentially expanded configuration.
 5. An endoprosthesis as inclaim 1, wherein the serpentine rings are sufficiently malleable so thatthey can be circumferentially expanded by applying a radially outwardforce from within the ring.
 6. An endoprosthesis as in claim 1, whereinthe supporting feature comprises a U-shaped connector.
 7. Anendoprosthesis as in claim 1, wherein the supporting feature comprises aV-shaped connector.
 8. An endoprosthesis as in claim 1, wherein thesupporting feature comprises an S-shaped connector.
 9. An endoprosthesisas in claim 1, wherein the supporting feature comprises a spiral-shapedconnector.
 10. An endoprosthesis as in claim 9, wherein thespiral-shaped connector has a ring core.
 11. An endoprosthesis as inclaim 9, wherein the spiral-shaped connector has a disk core.
 12. Anendoprosthesis as in claim 1, wherein the supporting feature comprises aW-shaped connector.
 13. An endoprosthesis as in claim 1, wherein thesupporting feature comprises an N-shaped connector.
 14. Anendoprosthesis as in claim 1, further comprising at least one additionalsupporting feature extending between at least some of the adjacentstruts.
 15. An endoprosthesis as in claim 1, wherein the supportingfeatures extend between midpoints on the adjacent struts.
 16. Anendoprosthesis as in claim 1, wherein the supporting features extendbetween points near the crowns on the adjacent struts.
 17. Anendoprosthesis as in claim 1, wherein said supporting features extendbetween two points on adjacent axial struts and one point on the crownwhich joins the struts.
 18. An endoprosthesis as in claim 1, whereinsaid supporting features have a cross-sectional area which is less thanthe cross-sectional area of the axial struts.
 19. An endoprosthesis asin claim 1, wherein at least some of the supporting features havedeflection points which preferentially yield when the serpentine ringsis circumferentially expanded.
 20. An endoprosthesis as in claim 19,wherein the deflection points comprise notches.
 21. An endoprosthesis asin claim 1, wherein the axial links comprise linear beams.
 22. Anendoprosthesis as in claim 21, wherein the linear beams are alignedaxially.
 23. An endoprosthesis as in claim 21, wherein the linear beamsare aligned at an angle relative to the axis.
 24. An endoprosthesiscomprising: a plurality of circumferentially expandable serpentinerings, each serpentine ring including axial struts joined by crowns,wherein the crowns act as hinges allowing the struts to spread as thering opens circumferentially; axial links joining at least some crownson adjacent rings; and supporting features extending between at leastsome adjacent axial links between adjacent serpentine rings, wherein thesupporting features elongate as the rings circumferentially expand. 25.An endoprosthesis as in claim 24, wherein the supporting featurecomprises a serpentine connector.
 26. An endoprosthesis as in claim 24,wherein the supporting feature comprises a box connector.